Method and system for preparing a solution

ABSTRACT

The present disclosure relates to a method for preparing a solution for use with a measuring device for determining a measurand that depends on a concentration of at least one analyte in a sample. The method includes a step of adding at least one capsule to a predetermined volume of a liquid comprising a solvent, wherein the capsule has a wall completely surrounding an interior and at least one substance accommodated within the interior. The wall of the capsule at least partially dissolves in the liquid and the substance accommodated in the interior escapes into the liquid. The method also includes a step of mixing the substance with the liquid or dissolving the substance in the liquid. The present disclosure also relates to a system for preparing a solution according to said method.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application is related to and claims the priority benefit of German Patent Application Nos. 10 2018 133 148.7, filed on Dec. 20, 2018 and 10 2019 130 236.6, filed on Nov. 8, 2019, the entire contents of which are incorporated herein by reference.

TECHNICAL FIELD

The present disclosure relates to a method and a system for preparing a solution for use with a measuring device which serves to determine a measurand that depends on a concentration of at least one analyte in a sample. The present disclosure also relates to a method for calibrating, verifying and/or adjusting such a measuring device.

SUMMARY

The object of analytical measuring in the laboratory and in the field of process measuring is the qualitative and/or quantitative determination of ingredients in measuring media, e.g. in measuring liquids. A wide range of measuring devices for measuring a multiplicity of different parameters are used for this purpose. In the field of liquid analysis, potentiometric sensors, such as pH measuring chains or ion-selective electrodes, amperometric sensors, conductivity sensors, optochemical sensors, photometers, spectrometers and analyzers are used, for example. Some measuring devices quantitatively determine a concentration of a single substance, for example an ion concentration, the pH value, the concentration of a dissolved gas, or the concentration of specific chemical compounds. Other measuring devices serve to determine sum parameters which include the concentration of a plurality of different substances, e.g. total organic carbon (TOC), total oxygen demand (CSB or COD), total nitrogen (TN), total phosphorus (TP), conductivity, or the spectral absorption coefficient (SAC).

In measuring mode, some measuring devices for liquid analysis require solutions which are used for measuring the measurand in samples of unknown composition and/or for calibrating, verifying or adjusting the measuring device. One example of such solutions are reagent solutions which serve to carry out a chemical reaction with the analyte in a sample before a measured value is detected.

Such reagent solutions are used, for example, in automatic analyzers. Analyzers are used, for example, for measuring the concentration of an analyte or of a sum parameter determined by a plurality of analytes. Analyzers are often designed to add one or more reagent solutions to a sample. The substances contained in the reagent solutions undergo a chemical reaction with the analyte or analytes, the reaction product of which can be detected by means of a measuring method. Frequently, the analyzer is configured to detect the reaction product optically, for example photometrically or spectrometrically, and to generate a measurement signal that correlates with the quantity of reaction product produced. This measurement signal can be used to determine the concentration of the analyte or the value of the sum parameter in the original sample. Such analyzers are known, for example, from DE 10 2013 114138 A1, DE 10 2013 114011 A1, DE 10 2011 075762 A1 or DE 10 2011 007011 A1.

So-called standard solutions are usually used for calibrating, verifying and adjusting the measuring devices, including the analyzers, mentioned here. “Calibrating a measuring device” is understood to mean ascertaining a deviation of the measured value measured by the measuring device from a value of the measurand that is assumed to be correct. This value that is assumed to be correct can be made available by a second measuring device which serves as standard. In addition to ascertaining the deviation, the verification also includes determining the deviation and evaluating it. “Adjusting” means adapting the measuring device in such a way that a measuring circuit and/or a model, by means of which the measuring device determines a measured value in the physical unit of the measurand from a primary measurement signal, for example a measuring voltage or a measuring current, is adapted such that the measured value determined corresponds to the value of the measurand that is assumed to be correct. Standard solutions used for the calibration of measuring devices for analytical measuring contain a predetermined quantity, for example a predetermined concentration, of one or more analytes to be determined by the measuring device to be calibrated. This predetermined analyte content of the standard solutions is used as a comparative value (measured value that is assumed to be correct) for the calibration, verification or adjustment of the measuring devices.

The composition of the liquids used by measuring devices of analytical engineering must be adjusted as precisely as possible in order to ensure correct results. This applies in a particularly high degree to the standard solutions used for calibration, verification and/or adjustment since a deviation of the actual concentration of the analyte or analytes in the standard solution from the desired concentration has a direct effect on the measuring accuracy of the measuring device.

High demands are therefore placed on the degree of purity of the starting materials used for the liquids. It is also necessary to work carefully and precisely in the preparation of the standard solutions. This requires suitable laboratory equipment, high training levels of the personnel entrusted with the preparation of the solutions, and elaborate quality control. Depending on which ingredients are to be added to the solution, corresponding occupational safety measures must be observed. It is therefore customary to prepare reagent solutions, standard solutions and other useful liquids of measuring devices in a specialized central laboratory and to send them ready-for-use to the users of the measuring devices. Measuring device manufacturers frequently also prepare reagent solutions and standard solutions for the calibration, adjustment and verification of their measuring devices and offer them as accessories or operating supplies for the corresponding measuring devices. However, some of these solutions are only temporarily stable, i.e., do not have a stable concentration, for example when they contain constituents which are degenerated or chemically converted under the influence of temperature, light or oxygen or by bacterial decomposition. Such standard solutions must frequently be renewed and possibly cannot be centrally manufactured and sent to the user in a ready-to-use form.

It is therefore desirable to prepare standard solutions immediately before their use for calibrating, verifying or adjusting a measuring device, possibly on site. Since the user of the measuring device must in this case as a rule prepare the standard solution, a method which is as simple, reliable and robust as possible should be available for the preparation of the standard solution. A few approaches in this respect are known in the prior art.

For example, the analyte and optionally further constituents of a standard solution, for example buffers or stabilizers, can be provided to the user in the form of a highly concentrated stock solution in a glass or plastic ampoule or bottle. The ampoule content must be transferred by the user to a volumetric flask, and a defined volume of a solvent, for example ultrapure water, must then be added. The advantage of this method is that the analyte is already present in the ampoule in the required quality and quantity. The user does not have to be concerned with the purity of the substances use, and measuring, for example weighing, the substances of the stock solution used from the ampoule is dispensed with. Nevertheless, there is a risk that the standard solution thus prepared does not contain the analyte at the required concentration since errors in measuring the solvent volume are possible. It can also happen that the ampoule content is not completely transferred into the volumetric flask if, for example, drops remain on the ampoule wall during the transfer. The correct handling of the ampoules requires trained personnel and corresponding quality control. Moreover, degeneration of the ampoule content by photochemically or thermally induced degradation processes cannot be completely ruled out in this method.

Reagent solutions comprising various substances which possibly react with one another under the influence of light and heat and thus have a limited shelf life, can be divided into a plurality of solid or liquid components which, when uncombined, have a long shelf life. This is known, for example, from DE 10 2011 007 011 A1, which describes an analyzer that is configured to automatically prepare a reagent solution from a plurality of components shortly before its use in the measuring device. To this end, the analyzer has a first reservoir with a first reagent component, a second reservoir with a second reagent component, and a mixing device for mixing a predetermined quantity of the first reagent component from the first reservoir with a predetermined quantity of the second reagent component from the second reservoir in order to form a predetermined quantity of the reagent solution. The reagent solution to be prepared, which itself does not have a long shelf life because its ingredients undergo degradation reactions, which may be thermally or photochemically induced, in solution, is thus divided for the purpose of storage into two reagent components, which in turn can comprise one or more individual chemical substances that, in the combination present in the respective reagent components, do not undergo any chemical decomposition reactions, or undergo chemical decomposition reactions taking place only very slowly under the conditions prevailing in the reservoirs.

According to the same principle, several ampoules, bottles or bags containing individual components of the solution to be prepared can be made available to a user for the preparation of reagent or standard solutions. Although this procedure prevents premature degeneration of the solutions, it also has the same disadvantages as the method described above, in which a single stock solution has to be diluted with solvent by the user.

The object of the present disclosure is therefore to specify an improved method for preparing a solution for use with a measuring device for determining a measurand that depends on a concentration of at least one analyte in a sample. In particular, the method should be able to be carried out with little effort by untrained or only slightly trained personnel and have a low risk of error.

This object is achieved by the method of the present disclosure, which includes calibrating, verifying and/or adjusting a measuring device for determining a measurand that depends on the concentration of at least one analyte in a sample. The present disclosure also includes a method for determining a measured value of a measurand that depends on the concentration of an analyte in a sample by means of a measuring device, and a system for preparing a solution for use with a measuring device for determining a measurand that depends on a concentration of at least one analyte in a sample.

The method of the present disclosure for preparing a solution for use with a measuring device for determining a measurand that depends on a concentration of at least one analyte in a sample includes adding at least one capsule to a predetermined volume of a liquid comprising a solvent, wherein the capsule has a wall completely surrounding an interior and at least one substance accommodated within the interior. The wall of the capsule at least partially dissolves in the liquid and the substance accommodated in the interior escapes into the liquid. The method also includes mixing the substance with the liquid and/or dissolving the substance in the liquid.

The substance is protected from contamination, oxygen and moisture by the wall of the capsule, which completely surrounds the interior. The capsule wall may also be designed to protect the substance from light. Prior to the addition of the capsule, the predetermined volume of the liquid comprising the solvent may also be stored in a closed and/or sealed manner in a suitable liquid container, such as a bottle, in order to protect this component from contamination, oxygen, light and moisture. Unlike the case of glass or plastic ampoules known from the prior art, the capsule does not have to be opened and emptied by the user but can be introduced as a whole into the liquid, where it dissolves at least partially so that the substance escapes into the liquid and dissolves therein. The loss of a portion of the substance is thus completely ruled out in the method according to the present disclosure, whereas substance can be lost during the opening of the ampoule and/or remain in the ampoule in a method of the prior art. Since the user also cannot accidentally come into contact with the substance enclosed in the capsule in the method according to the present disclosure, the risk of contamination is also greatly reduced, as are possible safety risks in the case of toxic or harmful substances.

The method permits a highly precise metering of the substance and can therefore be used for the preparation of any solutions for use with measuring devices of analytical engineering and particularly advantageously for the preparation of a standard solution for the calibration, verification and/or adjustment of measuring devices. In this application, the substance contains a predetermined quantity of the at least one analyte. However, the method is equally suitable for preparing other solutions for the measuring device, for example for preparing a reagent solution for carrying out a chemical reaction of a reagent contained in the reagent solution with the at least one analyte.

In a particularly advantageous embodiment, the predetermined volume of the liquid comprising the solvent is provided already measured in a closed, possibly also sealed, liquid container. In this case, the method comprises opening the liquid container prior to adding the capsule. In this embodiment of the method, an error of the user when measuring the components for the liquid to be prepared is practically ruled out.

In one embodiment of the present disclosure, the solution is a standard solution for calibrating, verifying and/or adjusting the measuring device, wherein the substance forms a first component of the standard solution, and wherein the liquid forms a second component of the standard solution. In this embodiment, the substance forming the first component may comprise a single chemical substance, for example the analyte. However, it is also possible for the substance to be a mixture of a plurality of chemical species, for example of various ions or molecules. Similarly, the second component may comprise one or more different chemical species. The components are advantageously divided in such a way that the substances present in one of the respective components do not undergo any chemical (decomposition) reactions or undergo chemical (decomposition) reactions which take place only very slowly with one another.

In a further embodiment, the substance may comprise a predetermined quantity of the analyte or a reactant which, upon mixing and/or dissolving the substance in the liquid, undergoes a chemical reaction which involves at least one second reactant contained in the liquid and in which the analyte forms as a reaction product.

In addition to the analyte or the reactant, the substance may comprise an extender which is inert to the further constituents of the solution to be prepared and does not influence the determination of measured values by the measuring device. Suitable extenders are, for example, sugar, starch or a silicate. Advantageously, the extender is soluble in the liquid, but this is not required. By means of the extender, the analyte or reactant is present in diluted form in the substance, for example in a ratio of 1:50 or 1:100 or 1:500. As a result, the filling accuracy of the analyte or reactant in the capsule can be improved. This is advantageous for the preparation of standard solutions with particularly low concentrations of the analyte.

In an alternative embodiment, the solution to be prepared can be a reagent solution to be added to the sample in order to measure the measurand, wherein the substance forms a first component of the reagent solution comprising one or more chemical substances, and wherein the liquid forms a second component of the reagent solution comprising one or more chemical substances. The components are advantageously divided in such a way that the substances present in one of the respective components do not undergo any chemical (decomposition) reactions or undergo chemical (decomposition) reactions which take place only very slowly with one another.

In an advantageous embodiment, the wall of the capsule is formed from a material which does not influence the determination of the measurand by means of the measuring device. This has the advantage that the measurement result obtained with the measuring device is independent of a mass or wall thickness of the capsule so that production fluctuations in the preparation of capsules for the method according to the present disclosure do not play any role in terms of the shape and wall thickness of the individual capsules.

If the solvent contained in the liquid is water, the wall of the capsule can be formed from a water-soluble and/or swellable material. For example, cellulose, gelatin, agar-agar or carrageenan may be used.

The substance may be present in the interior of the capsule as a solid, in a concentrated solution or bound to a solid phase. In the latter case, it may be bound to the solid phase by physisorption or chemisorption.

As already mentioned, the predetermined volume of the liquid can be provided in a closed liquid container. In this case, the capsule can be added to the volume of liquid presented in the liquid container and mixed with the liquid and/or dissolved in the liquid in the liquid container. The closed liquid container can be used for storage and/or transport for the predetermined volume of the liquid before the solution is prepared. In an advantageous embodiment, the liquid container can be sealed in the original state so that it is visible when the liquid container has already been opened once. After the first opening, the liquid container is re-closable so that it can serve for storing and transporting the prepared solution after the liquid has been prepared by adding the capsule to the liquid in the liquid container.

In an advantageous embodiment, the closed or sealed liquid container can contain an agitator body. This agitator body can be used for stirring or agitating the liquid in order to accelerate the dissolution of the substance. The agitator body can comprise a magnet which can be driven by a rotating magnetic field from outside the liquid container, e.g. by means of a magnetic stirrer or magnetic mixer, for stirring the liquid. By including the agitator body already in the closed or sealed liquid container any accidental contamination of the solution to be prepared by an agitator body added by a user to the liquid can be avoided.

The liquid may contain at least one stabilizer for inhibiting chemical or photochemical degradation reactions in the prepared solution.

The present disclosure also relates to a method for calibrating, verifying and/or adjusting a measuring device for determining a measurand that depends on a concentration of at least one analyte in a sample. This method includes preparing at least one standard solution by means of the method according to any of the above-described method embodiments, detecting by means of the measuring device at least one measured value of the measurand in at least a portion of the standard solution, and calibrating, verifying and/or adjusting the measuring device using the at least one measured value.

The volume of the liquid predetermined in the step of preparing the standard solution may be presented in a closable or closed liquid container. In this case, the capsule can be added directly to the volume of the liquid provided in the liquid container possibly after the opening of the liquid container, where applicable, and the substance escaping from the capsule can be mixed with the liquid and/or dissolved in the liquid in the liquid container. The liquid container can be closed again after opening and adding the capsule. This is advantageous if the measuring device is an automatic analyzer because the liquid container can serve both as a transport and storage container for the standard solution and can also be used directly as a standard solution reservoir in the analyzer. This saves intermediate steps for transferring the liquid or the prepared standard solution and avoids loss of liquid.

The method may also include steps of connecting the liquid container to a liquid line fluidly connected to a reaction vessel of the analyzer, metering at least one predetermined volume of the standard solution contained in the liquid container into the reaction vessel via a liquid line, and performing a chemical reaction of the analyte contained in the solution with at least one reaction partner supplied to the reaction vessel in order to form a reaction product. Further, the method includes detecting a measured value dependent on the quantity of the reaction product formed.

For calibration, verification or adjustment, the method further includes comparing the measured value with a reference measured value representing the concentration of the analyte in the standard solution that is assumed to be correct. This reference measured value can be determined from the volume of the liquid used for preparing the standard solution and the quantity of analyte contained in the capsule.

The present disclosure also includes a method for determining by means of a measuring device a measured value of a measurand that depends on the concentration of an analyte in a sample liquid. This method is based on the standard addition method known per se. The capsule which can be used for the above-described method for preparing a solution, such as a standard solution, can accordingly also be used for adding a defined quantity of the analyte to an unknown sample liquid in order to determine an analyte concentration according to the standard addition method.

The method for determining a measured value of the measurand by means of a standard addition method includes adding a specific quantity of analyte to the sample liquid or to samples taken from the sample liquid, wherein the analyte is added in the form of at least one capsule, wherein the capsule has a wall completely surrounding an interior and a substance comprising the analyte and accommodated within the interior, and wherein the wall of the capsule dissolves at least partially in the sample liquid, and the substance accommodated in the interior escapes into the sample liquid and dissolves therein.

According to one embodiment, the method includes dividing a sample liquid into at least a first, a second and a third sample, such as in the same volumes, and detecting by means of the measuring device a first measurement signal representing the measurand in the first sample. The method also includes adding to the second sample at least one first capsule which has a wall completely surrounding an interior and a substance accommodated within the interior and comprising at least one predetermined quantity of the analyte, wherein the wall of the first capsule at least partially dissolves in the second sample and the substance accommodated in the interior escapes into the second sample, and mixing the substance with the second sample and/or dissolving the substance in the second sample. After adding the at least one first capsule to the second sample, the method includes, detecting by means of the measuring device a second measurement signal representing the measurand in the second sample.

The method also includes adding at least one second capsule to the third sample, wherein the wall of the second capsule at least partially dissolves in the third sample and the substance accommodated in the interior escapes into the third sample, and mixing the substance with the third sample and/or dissolving the substance in the third sample, wherein the quantity of analyte added to the third sample by addition of the at least one second capsule differs from the quantity of the analyte added to the second sample by addition of the at least one first capsule. After adding the at least one second capsule, the method includes detecting by means of the measuring device a third measurement signal representing the measurand in the third sample. Further, the method includes deriving a measured value of the measurand on the basis of the first, the second and the third measurement signal.

This embodiment is suitable for measuring devices which consume the sample in order to detect a measurement signal, for example for the analyzers already mentioned above, which add to a sample one or more reagents for carrying out a chemical reaction or which chemically or thermally digest a sample in order to detect a measurement signal in the sample. A plurality of first capsules may be added to the second sample and a plurality of second capsules may be added to the third sample. It is also conceivable that in each case only one first capsule is added to the second sample and one second capsule is added to the third sample, in which case the first and the second capsule contain different quantities of the analyte.

The sample liquid is, for example, a liquid water sample, e.g. drinking water or waste water, in which the wall of the capsule at least partially dissolves.

In another embodiment, which is suitable for measuring devices which do not consume the sample liquid in the measurement, for example for ion-selective electrodes, conductivity sensors, pH sensors, or optical or spectrometric probes, the method may include detecting by means of the measuring device a first measurement signal representing the measurand in a sample taken from the sample liquid, and adding to the sample at least one first capsule which has a wall completely surrounding an interior and a substance accommodated within the interior and comprising at least one predetermined quantity of the analyte, wherein the wall of the capsule at least partially dissolves in the sample and the substance accommodated in the interior escapes into the sample, and mixing the substance with the sample and/or dissolving the substance in the sample.

The method further includes detecting by means of the measuring device at least one second measurement signal representing the measurand in the sample, and adding to the sample at least one second capsule which has a wall completely surrounding an interior and a substance accommodated within the interior and comprising at least one predetermined quantity of the analyte, wherein the wall of the capsule at least partially dissolves in the sample and the substance accommodated in the interior escapes into the sample, and mixing the substance with the sample and/or dissolving the substance in the sample.

Thereafter the method includes detecting by means of the measuring device at least one third measurand signal representing the measurand in the sample, and deriving a measured value of the measurand on the basis of the first, the second and the third measurement signal.

In this embodiment, the first and the second capsule are advantageously designed identically and contain the same quantity of the analyte. However, it is also possible to use capsules which contain different quantities of the analyte, provided this is taken into account when deriving the measured value of the measurand.

In both method embodiments, the measured value of the measurand can be determined by extrapolation of a function representing the sequence of the measurement signals or the sequence of values derived from the measurement signals depending on the concentration of the analyte, e.g. a best-fit straight line.

In all method variants described here, it is possible to detect more than three measurement signals and to derive therefrom the measured value of the measurand. For this purpose, further samples can be prepared with analyte added by adding capsules. In the case of a measurement without sample consumption, further measurement signals can be detected with the measuring device after adding further analyte-containing capsules to the sample. The further measurement signals can then additionally be used for determining the best-fit straight line and for determining the unknown analyte concentration of the sample or sample liquid.

The present disclosure also relates to a system for preparing a solution for use with a measuring device for determining a measurand that depends on a concentration of at least one analyte in a sample, with the system including at least one first capsule having a wall completely surrounding an interior and at least one first substance accommodated within the interior. The system also includes a liquid container, which may be closed in a liquid-tight manner, which contains a predetermined volume of a liquid containing a solvent. The wall may be designed to at least partially dissolve in the solvent.

As already mentioned in connection with the above-described method for preparing a solution for use with a measuring device for determining a measurand that depends on a concentration of at least one analyte in a sample, the solution can be, for example, a standard solution for the calibration, verification and/or adjustment of the measuring device or another solution to be used with the measuring device, e.g. a reagent solution to be added to the sample in order to carry out a measurement.

As already described in connection with the preparation method for the solution, the solution to be prepared can be divided into a plurality of components, wherein one component is formed by the liquid and one or more further components can be present in the form of a substance contained in one or more capsules.

The first substance may form a first component of the solution, and the liquid may form a second component of the solution. As already mentioned above in connection with the method, the two components can each comprise one or more chemical substances.

The first substance may comprise a predetermined quantity of the analyte or of a first reactant which, upon mixing and/or dissolving the substance in the liquid, undergoes a chemical reaction which involves at least one second reactant contained in the liquid and in which the analyte forms as a reaction product.

In addition to the analyte or the first reactant, the substance may comprise an extender which is inert to the further constituents of the solution to be prepared and also does not influence the determination of measured values by the measuring device. Advantageously, the extender is soluble in the liquid, but this is not required.

The second reactant may be present in the liquid from the outset. However, it is also possible for the system to additionally comprise at least one second capsule which has a wall completely surrounding an interior and at least one second substance accommodated within the interior, wherein the wall of the second capsule is designed to dissolve at least partially in the solvent, and wherein the second substance comprises the second reactant. In this case, in order to prepare the solution, both capsules are added simultaneously or successively to the liquid so that both reactants dissolve in the liquid. The chemical reaction by which the analyte is formed then takes place during or after dissolution of the first and the second reactant in the liquid. The substance contained in the second capsule may also comprise an inert extender in addition to the second reactant.

If the system is configured to prepare a reagent solution to be added to a sample, the substance contained in the first capsule may comprise a first substance which is intended for carrying out a chemical reaction with the analyte.

The at least one first capsule of the system or all of the capsules belonging to the system can be enclosed in an outer packaging in a gas-tight and liquid-tight manner.

The at least one first capsule of the system or all of the capsules belonging to the system can be accommodated in a blister packaging which has a flexible rear wall on which the at least one first capsule rests and a plastic film molding which is integrally bonded to the flexible rear wall in such a way that the plastic film molding and the rear wall form a closed chamber in which the at least one first capsule is arranged.

The liquid may be contained in a closed liquid container. The closure can be secured and/or sealed, for example in such a way that it is visible when the bottle has already been opened. In an advantageous embodiment the closed and sealed liquid container can include an agitator body, which can be used to stir the liquid in order to accelerate the dissolution of the substance in the liquid. The agitator body can comprise a magnet, such as a permanent magnet, which can be driven by means of a magnetic field from outside the liquid container. As described above, by providing an agitator body already included in the liquid container of the system any accidental contamination of the liquid resulting from a contaminated agitator added to the liquid container by a user is avoided.

The components which are packaged in this way and which are to be brought together to prepare the solution can be marked on the packaging by the manufacturer. Safety instructions, recommendations for use, expiry dates or other information on the components and their use may also be printed on the packaging. This allows traceability of the prepared solutions. Since the user does not make any further changes to the composition of the individual components but only brings them together, quality fluctuations can be identified on the basis of the identifiers on the packagings and traced back to the manufacturer of the components. Alternatively or additionally, the individual capsules may also be marked.

The liquid may advantageously contain a stabilizer for inhibiting chemical or photochemical degradation reactions in the prepared solution.

BRIEF DESCRIPTION OF THE DRAWINGS

The present disclosure is explained in further detail below on the basis of the exemplary embodiments shown in the figures. They show:

FIG. 1a shows a schematic representation of a system for preparing a solution for use with a measuring device according to a first exemplary embodiment;

FIG. 1b shows a schematic representation of a capsule of the system according to FIG. 1 a;

FIG. 1c shows a schematic representation of a blister packaging with a plurality of capsules of the system shown in FIG. 1 a;

FIG. 2 shows a schematic representation of a measurement setup for a standard addition method for determining a concentration of an analyte in a sample of unknown composition;

FIG. 3 shows a graphical representation of concentration measured values detected with the measurement setup shown in FIG. 2; and

FIG. 4 shows a schematic representation of the structure of an analyzer for determining the concentration of an analyte.

DETAILED DESCRIPTION

FIGS. 1a and 1b schematically illustrate a system 1 for preparing a solution for use with a measuring device for determining a measurand that depends on the concentration of an analyte in a sample. Such a measuring device is also referred to below as an analysis measuring device. In the exemplary embodiment described here, the solution is a standard solution for the calibration, verification and/or adjustment of an analysis measuring device. In the example shown here, the system 1 comprises a closable liquid container 2 with a removable screw cap 3 in which a liquid 5 is contained, and a capsule 4. The capsule 4 is shown in FIG. 1b in an enlarged detailed view. The capsule 4 consists of a wall which completely surrounds an interior and which, in the exemplary embodiment shown here, is composed of two halves. The interior contains a substance 6, which is in the form of a solid powder in the present example. The substance 6 and the liquid 5 contained in the liquid container 2 form two components of the standard solution to be prepared. Both components can be stored separately from one another in the system 1.

In the present example, the substance 6 contains a predetermined quantity of the analyte, the concentration of which can be determined by means of the analysis measuring device after combination with the liquid 5. If the analysis measuring device is, for example, an analyzer, for example for determining the phosphate content of a sample, the capsule 4 may contain a phosphate salt. Optionally, the substance 6 may contain further constituents, for example an adsorbent which is indifferent to the analysis, for example diatomaceous earth, or further constituents, such as stabilizers or buffers or an extender. The liquid 5 contains a solvent in which the substance 6 is soluble. This solvent can be water, for example. In addition, the liquid 5 may contain further constituents, for example stabilizers or buffers. The volume of the liquid contained in the liquid container is exactly defined. It can be matched to the quantity of analyte contained in the capsule 4 in such a way that a specific analyte concentration is produced by dissolving the substance 6 in the liquid 5. The wall of the capsule 4 is formed of a material which is at least partially soluble in water and which does not influence the determination of the analyte by the analysis measuring device. Gelatin, for example, is suitable.

In order to prepare the standard solution, the screw cap 3 is removed from the liquid container 2, and the capsule 4 is placed in the liquid container 2. The liquid container 2 can then be closed again. The wall of the capsule 4 dissolves in the liquid 5 so that the substance 6 escapes into the liquid 5 and dissolves therein. In order to accelerate the dissolution of the capsule 4 and the dissolution of the substance 6 in the liquid 5, the liquid container 2 can be shaken, stirred and/or heated. An agitator body (not shown) can be included in the closed liquid container 2. For example, the agitator body can be embodied as a permanent magnet, so that it can be driven to a rotational movement by a rotating magnetic field from outside the liquid container 2. The rotating magnetic field can be provided by a magnetic stirrer.

The preparation of the standard solution by means of the system 1 is very simple. The capsule 4 with the predetermined quantity of the analyte contained in the substance 6 and the liquid container 2 with the already measured volume of the liquid can be made available to a user. In this case, the user does not need to measure the substance quantities used for the preparation of the standard solution. Since the capsule 4 as a whole is placed in the liquid 5 already present in the liquid container 2, there is no risk of errors occurring during the mixing of the components due to the loss of residues, remaining in a packaging or ampoule, of the substances used.

In a variation of the method, it is also possible for two or more capsules 4 containing the same substance 6 to be dissolved in the liquid 5 provided in the liquid container 2 in order to obtain a standard solution of higher concentration. On the other hand, the prepared standard solution can also be further diluted in a subsequent step by adding a specific volume of the solvent.

An advantageous packaging of the capsule 4 of the system 1 shown in FIGS. 1a and 1b is shown in FIG. 1 c. Shown schematically in this case is a blister packaging 7 in which a plurality of identical capsules 4 are packed together. The capsules 4 in the example described here contain the same substance 6, each containing the same predetermined quantity of analyte. In another embodiment, it is also possible for the capsules contained in the blister packaging to contain different quantities of the analyte. It is also possible to mark the packaging or the individual capsules in order to assign an individual serial number and an individual substance quantity to each capsule. The label may also be machine-readable (e.g. a barcode). Traceability may thereby be optimized. The blister packaging 7 has a flexible rear wall on which the capsules 4 rest. The rear wall can consist, for example, of cardboard or a metal foil. The capsules 4 are fixed by a plastic film molding which is integrally bonded in an edge region to the flexible rear wall so that the plastic film molding and the rear wall form a gas-tight chamber for each of the capsules 4 in each case. The capsules 4 are thus protected from oxygen and moisture, for example.

A plurality of variations of the exemplary embodiment described here is conceivable: The system and method described here can also be used, for example, for preparing solutions other than standard solutions, such as for preparing reagent solutions for an analyzer. In the example described here, only a single capsule is used. However, it is also possible that the solution to be prepared is prepared from more than two different components. For example, two or more capsules with different substances can be dissolved in a predetermined quantity of a liquid. A corresponding system suitable for this method comprises a single blister packaging 7 in which all the capsules to be used are combined. The liquid container 2 with the liquid 5 does not necessarily have to be provided as a package with the capsules 4. In a variation of the exemplary embodiment, it is also possible for the user to measure the liquid 5 during the preparation of the standard solution and to present it in a container before adding the capsule 4.

FIG. 2 schematically shows a measurement setup for determining a measurand that depends on the concentration of an analyte in a sample according to the standard addition method. The measurement setup comprises a measuring device 10 with a probe 11 and a measurement transducer 12 connected to the probe 11. A container 13 contains a liquid sample 14 of unknown composition. The probe 11 dips into the sample 14 in order to detect measured values. In the present exemplary embodiment, the probe 11 is an ion-selective electrode for measuring ammonium. It produces a measuring voltage that depends on the ammonium concentration in the sample and outputs it to the measurement transducer 12 for further processing. In order to carry out a standard addition method, a plurality of capsules 4 can now be added successively to the sample, each containing a substance having a predetermined quantity of the analyte, in this case an ammonium salt. After each capsule 4 is added and dissolved, a new measurement signal is detected. This measurement signal characteristic is shown in FIG. 3. In the diagram, the concentration c of the sample is plotted on the abscissa and the measurement signal S (here: measuring voltage) supplied by the measuring device 10 is plotted on the ordinate. The measurement signal plotted at cu was detected in the sample without addition. The measurement signal plotted at concentration c1 was detected after addition to the sample and dissolution of a first capsule 4, the measurement signal plotted at concentration c2 was detected after addition to the sample and dissolution of a further, identical capsule 4, and the measurement signal plotted at concentration c3 was detected after addition to the sample and dissolution of a third identical capsule. By linear regression, a best-fit straight line can be determined based on the measuring points detected for the concentrations c1, c2, c3, and the zero point and the value of cu based thereon can be determined by extrapolation of the straight line.

The method described here with reference to FIG. 2 is suitable for measurements according to the standard addition method with measuring devices which do not consume the sample during the measurement. These are, for example, electrochemical sensors, such as potentiometric or amperometric sensors, e.g. ion-selective electrodes or pH sensors, conductivity sensors or photometric or spectrometric measuring probes.

On the other hand, measurements with analyzers are carried out while consuming the sample. In this case, the sample liquid to be examined is divided into a plurality of individual samples, and a measurement signal corresponding to the measurement signal at the unknown concentration cu is detected with a first sample. In each case, different quantities of the analyte or analytes are added to further samples by respectively adding a different number of identical capsules 4 to the individual parts of the sample. The analyzer can then detect further measurement signals with the further samples. The obtained measurement signals are then plotted completely analogously to the diagram shown in FIG. 3, and a best-fit straight line is determined and extrapolated. The value of the unknown concentration cu can be determined by the extrapolation.

FIG. 4 shows an analyzer 100 which uses two standard solutions for calibration and/or adjustment prepared according to the method described in connection with FIGS. 1a and 1 b. The analyzer 100 is connected to a sample receiver 21 containing a sample liquid from which it removes a sample in each case in order to detect a measured value of a measurand that depends on the concentration of an analyte. The analyzer has a measuring cell 22 which is connected to the sample receiver 21 via a fluid line 23. The analyzer further comprises a first liquid container 24 which contains a reagent solution. The liquid container 24 is connected to the measuring cell 22 via a further liquid line 25. Lastly, the analyzer 100 has two further liquid containers 2.1 and 2.2, each containing a standard solution. The liquid container 2.1 contains the analyte in a first concentration, and the liquid container 2.2 contains the analyte in a second concentration different therefrom. Both liquid containers 2.1, 2.2 are fluidly connected to the measuring cell 22.

The standard solutions contained in the liquid containers 2.1, 2.2 were prepared by adding one or more capsules 4 to a fixedly predetermined volume of a liquid 5 already presented in the liquid containers 2.1, 2.2 and by at least partially dissolving in the liquid 5 the capsule wall and the substance contained therein and containing the analyte. The same liquid volume was presented in both liquid containers 2.1, 2.2 in the present example. In order to produce a higher concentration in the liquid container 2.2, a larger number of capsules 4 was added to the liquid volume. After the standard solutions have been prepared, the liquid containers 2.1 and 2.2, which were originally used as storage containers for the liquid 5, now serve as reservoirs of the analyzer and are connected to its measuring cell 22 via fluid lines 28, 29.

In addition to the fluid lines 23, 28, 29, 25, the analyzer 100 comprises valves and/or pumps for transporting the sample, the standard solutions and the reagent solution (not shown in FIG. 4). The analyzer 100 has an electronic control and measuring system 26 for controlling the valves and pumps and for detecting and processing measured values. The measuring cell 22 has a sensor 27 which is designed to carry out a photometric measurement in a liquid contained in the measuring cell 22, and to output detected measurement signals to the electronic control and measuring system 26.

In order to detect a measured value, the electronic control and measuring system 26 transports a sample from the sample receiver 21 into the measuring cell 22 and adds a predetermined quantity of the reagent solution contained in the liquid container 24 to the sample via the fluid line 25. A chemical reaction takes place in the liquid mixture thus formed, which results in a reaction product. By means of the sensor 27, the electronic control and measuring system 26 detects a measurement signal of the sensor 27 that depends on the concentration of the reaction product and determines a measured value of the measurand based on the measurement signal. After the measured value has been determined, the spent liquid is discharged again from the measuring cell 22 via a discharge line 30.

The measured value of the measurand is determined from the measurement signal by means of a calibration function which assigns measured values to values of the measurement signal. The calibration function can be checked (calibrated or verified) or adapted (adjusted) from time to time by means of the standard solutions. For this purpose, the electronic control and measuring system 26 can transport standard solution from the liquid container 2.1 or the liquid container 2.2 into the measuring cell 22 instead of a sample from the sample receiver 21 and detect a measured value of the measurand in a completely analogous manner as described above for the sample. A calibration, verification or adjustment can be carried out on the basis of a comparison of the reference value of the measurand that is known for the standard solutions and assumed to be correct with the measured value determined by the electronic control and measuring system. Since the standard solutions in the liquid containers 2.1 and 2.2 are prepared according to the simple and little error-prone method described above, the calibration, verification and adjustment of the analyzer with these standard solutions is also little error-prone and allows reliable measurement operation with little maintenance effort. 

1. A method for preparing a solution for use with a measuring device for determining a measurand that depends on a concentration of at least one analyte in a sample, including: adding at least one capsule to a predetermined volume of a liquid comprising a solvent, wherein the capsule has a wall completely surrounding an interior and at least one substance accommodated within the interior, wherein the wall of the capsule at least partially dissolves in the liquid and the substance accommodated in the interior escapes into the liquid; and mixing the substance with the liquid and/or dissolving the substance in the liquid.
 2. The method of claim 1, wherein the solution is a standard solution for calibrating, verifying or adjusting the measuring device, and wherein the substance forms a first component of the standard solution, and wherein the liquid forms a second component of the standard solution.
 3. The method of claim 1, wherein the substance comprises a predetermined quantity of the analyte or of a first reactant which, upon mixing or dissolving the substance in the liquid, undergoes a chemical reaction which involves at least one second reactant contained in the liquid and in which the analyte forms as a reaction product.
 4. The method of claim 1, wherein the solution is a reagent solution to be added to the sample in order to measure the measurand, and wherein the substance forms a first component of the reagent solution comprising one or more chemical substances, and wherein the liquid forms a second component of the reagent solution comprising one or more chemical substances.
 5. The method of claim 1, wherein the wall of the capsule is formed from a material which does not influence the determination of the measurand by means of the measuring device.
 6. The method of claim 1, wherein the substance is present in the interior of the capsule as a solid or bound to a solid phase.
 7. The method of claim 1, wherein the predetermined volume of the liquid is presented in a closed liquid container, wherein the liquid container is opened, the capsule is added to the volume of the liquid presented in the liquid container, and the substance escaping from the capsule is mixed with the liquid or dissolved in the liquid in the liquid container.
 8. The method of claim 1, wherein the liquid contains at least one stabilizer for inhibiting chemical or photochemical degradation reactions of the analyte or of the substance intended for carrying out a chemical reaction with the analyte in the prepared solution.
 9. A method for calibrating, verifying or adjusting a measuring device for determining a measurand that depends on a concentration of at least one analyte in a sample, including: preparing at least one standard solution by: adding at least one capsule to a predetermined volume of a liquid comprising a solvent, wherein the capsule has a wall completely surrounding an interior and at least one substance accommodated within the interior, wherein the wall of the capsule at least partially dissolves in the liquid and the substance accommodated in the interior escapes into the liquid; and mixing the substance with the liquid or dissolving the substance in the liquid; detecting by means of the measuring device at least one measured value of the measurand in at least a portion of the standard solution; and calibrating, verifying and/or adjusting the measuring device using the at least one measured value.
 10. The method of claim 9, wherein the volume of the liquid predetermined in the step of preparing the standard solution is presented in a closable liquid container, the capsule is added to the volume of the liquid presented in the liquid container, and the substance escaping from the capsule is mixed with the liquid or dissolved in the liquid in the liquid container, and wherein the measuring device is an analyzer, and wherein the method further comprises the following steps: connecting the liquid container to a liquid line fluidly connected to a reaction vessel of the analyzer; metering at least one predetermined volume of the standard solution contained in the liquid container into the reaction vessel via a liquid line; performing a chemical reaction of the analyte contained in the standard solution with at least one reaction partner supplied to the reaction vessel in order to form a reaction product; and detecting a measured value dependent on the quantity of the reaction product formed.
 11. A method for determining a measured value of a measurand that depends on the concentration of an analyte in a sample liquid by means of a measuring device according to a standard addition method, including: using a measuring device according to a standard addition method to determine the measured value; adding a specific quantity of analyte in the form of at least one capsule to the sample liquid or to samples taken from the sample liquid; wherein the capsule has a wall completely surrounding an interior and a substance accommodated within the interior and comprising the analyte; and dissolving the wall of the capsule at least partially in the sample liquid, and the substance and the substance accommodated in the interior escapes into the sample liquid and dissolves therein.
 12. The method of claim 11, including: detecting, using the measuring device, a first measurement signal representing the measurand in a sample taken from the sample liquid; adding to the sample at least one first capsule which has a wall completely surrounding an interior and a substance accommodated within the interior and comprising at least one predetermined quantity of the analyte, wherein the wall of the capsule at least partially dissolves in the sample and the substance accommodated in the interior escapes into the sample, and mixing the substance with the sample or dissolving the substance in the sample; detecting, using the measuring device, at least one second measurement signal representing the measurand in the sample; adding to the sample at least one second capsule having a wall completely surrounding an interior and a substance accommodated within the interior and comprising at least one predetermined quantity of the analyte, wherein the wall of the capsule at least partially dissolves in the sample and the substance accommodated in the interior escapes into the sample, and mixing the substance with the sample or dissolving the substance in the sample; detecting, using the measuring device, at least one third measurement signal representing the measurand in the sample; and deriving a measured value of the measurand on the basis of the first, the second and the third measurement signal.
 13. The method of claim 11, wherein the measured value of the measurand is determined by extrapolation of a function representing the sequence of the measurement signals or the sequence of values derived from the measurement signals depending on the concentration of the analyte.
 14. A system for preparing a solution for use with a measuring device for determining a measurand that depends on a concentration of at least one analyte in a sample, including: at least one first capsule which has a wall completely surrounding an interior and at least one first substance accommodated within the interior; and a container closed in a liquid-tight manner, which contains a predetermined volume of a liquid containing a solvent; wherein the wall is designed to at least partially dissolve in the solvent.
 15. The system of claim 14, wherein the solution is a standard solution for calibrating, verifying or adjusting the measuring device.
 16. The system of claim 14, wherein the first substance forms a first component of the standard solution, and wherein the liquid forms a second component of the standard solution.
 17. The system of claim 15, wherein the first substance comprises a predetermined quantity of the analyte or of a first reactant which, upon mixing or dissolving the substance in the liquid, undergoes a chemical reaction which involves at least one second reactant contained in the liquid and in which the analyte forms as a reaction product.
 18. The system of claim 17, further comprising at least one second capsule which has a wall completely surrounding an interior and at least one second substance accommodated within the interior, wherein the wall of the second capsule is designed to at least partially dissolve in the solvent, and wherein the second substance comprises the second reactant.
 19. The system of claim 14, wherein the at least one first capsule is enclosed in an outer packaging in a gas-tight and liquid-tight manner.
 20. The system of claim 14, wherein the at least one first capsule is accommodated in a blister packaging which has a flexible rear wall on which the at least one first capsule rests and a plastic film molding which is integrally bonded to the flexible rear wall in such a way that the plastic film molding and the rear wall form a closed chamber in which the at least one first capsule is arranged. 